Research will be undertaken to employ ion and gas sensing membrane electrodes for clinical analysis of substrates, enzymes, electrolytes, and other body fluid constituents. Methods will be developed for the determination of clinically important substances in serum, whole blood, and urine involving the employment of crystal membrane, enzyme coated and other electrodes in continuous analysis systems with capabilities of handling 100-200 samples per hour. It is expected that the proposed approach will result in desirable simplifications of the chemistries involved, by elimination of dialysis and color development steps, and will produce a significant reduction in analysis costs, by the elimination of expensive optical and electronic instrumentation as well as a reduction in the quantities and number of required reagents. A further part of the proposed research is directed toward the development and evaluation of micro electrodes as biological probes with tip sizes below 5 microns in diameter. It is expected that these micro probes will be useful in sub-microliter samples, as continuous sensors in fluid streams, and as direct probes for measurements in small organs and cells. Finally, it is proposed to develop enzyme electrode probes selective for creatinine, adenosine monophosphate, and uric acid for direct measurement in body fluids, including whole blood.